Thermal and substrate color-induced melanization in laboratory reared red-eared sliders (Trachemys scripta elegans).

Color and pigmentation patterns of the integument can facilitate crypsis, thermoregulation, and social signaling. According to the "thermal melanism hypothesis", cold environmental temperature should increase the quantity of melanin that is deposited in the integument thereby facilitating radiative warming. We studied the influences of water temperature (26°C or 31°C) and substrate color (black or white) on the degree of melanization in the red-eared slider, Trachemys scripta elegans, under laboratory conditions. Turtles reared on a black substrate, or in 26°C water, for 120 days were darker than those reared on a white substrate or in 31°C water. A potential tradeoff between the fitness benefits of crypsis and the benefits of radiative warming through melanism was detected because turtles reared in 26°C water and on a white substrate were darker than those reared on a white substrate and in 31°C water. Low temperatures limited metabolic processes because turtles reared in 26°C water grew more slowly than those reared in 31°C water. However, histological analyses revealed that melanization was a dynamic process in all treatments confirming that the degree of melanization in the cool water treatment was not influenced by the initial and relatively dark hatchling coloration in individuals that grew relatively slowly.

A novel approach to deep venous arterialization using WavelinQ EndoAVF technology.

Deep venous arterialization is increasingly being considered for the management of patients with "no option chronic limb threatening ischemia" (CLTI) who would otherwise require a major limb amputation. WavelinQ (Becton Dickinson) is a new technology increasing in popularity for its role in the formation of endovascular arteriovenous fistulas but might well have applications in other areas of vascular surgery. We present a novel approach to deep venous arterialization using WavelinQ arteriovenous fistula technology for a patient with nonreconstructable chronic limb threatening ischemia experiencing both rest pain and forefoot gangrene. The patient's early tissue loss healed and he remained symptom free at 6 months after the intervention.

Trafficking of cholesterol to the ER is required for NLRP3 inflammasome activation.

Cellular lipids determine membrane integrity and fluidity and are being increasingly recognized to influence immune responses. Cellular cholesterol requirements are fulfilled through biosynthesis and uptake programs. In an intricate pathway involving the lysosomal cholesterol transporter NPC1, the sterol gets unequally distributed across intracellular compartments. By using pharmacological and genetic approaches targeting NPC1, we reveal that blockade of cholesterol trafficking through the late endosome-lysosome pathway blunts NLRP3 inflammasome activation. Altered cholesterol localization at the plasma membrane (PM) in Npc1-/- cells abrogated AKT-mTOR signaling by TLR4. However, the inability to activate the NLRP3 inflammasome was traced to perturbed cholesterol trafficking to the ER but not the PM. Accordingly, acute cholesterol depletion in the ER membranes by statins abrogated casp-1 activation and IL-1ß secretion and ablated NLRP3 inflammasome assembly. By contrast, assembly and activation of the AIM2 inflammasome progressed unrestricted. Together, this study reveals ER sterol levels as a metabolic rheostat for the activation of the NLRP3 inflammasome.